Wild waterfowl, the natural hosts of all known influenza A viruses, are the source of viruses which cause sporadic outbreaks of highly fatal disease in domestic poultry. Since 1997, highly pathogenic (HP) avian influenza A H5N1 viruses have caused a series of outbreaks in Hong Kong, and most recently in 9 other Asian countries. As human exposure to and infection with H5N1 viruses continues to increase, so too does the likelihood of the generation of an avian-human reassortant virus which may transmit efficiently within the human population which lacks HA-specific immunity to H5N1 viruses. In 1997, HPAl H5N1 in Hong Kong resulted in transmission from poultry to humans, resulting in 18 infected people and six deaths. In 2003- 2005, extensive outbreaks of highly pathogenic avian influenza A (H5N1) occurred in several Asian countries (Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand and Vietnam, North Korea), resulting in 17 human cases in Thailand and 27 in Vietnam and 3 in Cambodia; there were 51 reported deaths. H5N1 infections in family clusters have raised the possibility of human-to-human transmission of H5N1 virus. We have recently developed an adenoviral-based influenza vaccine encoding the hemagglutinin (HA) antigen of the A/Vietnam/1203/2004 (H5N1) strain isolated during the 2003-2005 lethal human outbreak. Vaccinated mice and chickens had broad virus-specific cellular and humoral immunity and were fully protected from a lethal intranasal H5N1 challenge, whereas all control animals died within few days. Hence, a centralized and integrated clinical vaccine testing will be proposed. [unreadable] [unreadable] [unreadable]